| Title : Discovery of 4-(5-(4-chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744) as a novel positive allosteric modulator of the alpha7 nicotinic acetylcholine receptor - Faghih_2009_J.Med.Chem_52_3377 |
| Author(s) : Faghih R , Gopalakrishnan SM , Gronlien JH , Malysz J , Briggs CA , Wetterstrand C , Ween H , Curtis MP , Sarris KA , Gfesser GA , El-Kouhen R , Robb HM , Radek RJ , Marsh KC , Bunnelle WH , Gopalakrishnan M |
| Ref : Journal of Medicinal Chemistry , 52 :3377 , 2009 |
|
Abstract :
The discovery of a series of pyrrole-sulfonamides as positive allosteric modulators (PAM) of alpha7 nAChRs is described. Optimization of this series led to the identification of 19 (A-867744), a novel type II PAM with good potency and selectivity. Compound 19 showed acceptable pharmacokinetic profile across species and brain levels sufficient to modulate alpha7 nAChRs. In a rodent model of sensory gating, 19 normalized gating deficits. These results suggest that 19 represents a novel class of molecules capable of allosteric modulation of the alpha7 nAChRs. |
| PubMedSearch : Faghih_2009_J.Med.Chem_52_3377 |
| PubMedID: 19419141 |
Faghih R, Gopalakrishnan SM, Gronlien JH, Malysz J, Briggs CA, Wetterstrand C, Ween H, Curtis MP, Sarris KA, Gfesser GA, El-Kouhen R, Robb HM, Radek RJ, Marsh KC, Bunnelle WH, Gopalakrishnan M (2009)
Discovery of 4-(5-(4-chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744) as a novel positive allosteric modulator of the alpha7 nicotinic acetylcholine receptor
Journal of Medicinal Chemistry
52 :3377
Faghih R, Gopalakrishnan SM, Gronlien JH, Malysz J, Briggs CA, Wetterstrand C, Ween H, Curtis MP, Sarris KA, Gfesser GA, El-Kouhen R, Robb HM, Radek RJ, Marsh KC, Bunnelle WH, Gopalakrishnan M (2009)
Journal of Medicinal Chemistry
52 :3377